On December 14, 2021 City of Hope, a world-renowned cancer research and treatment organization, reported study results of a Phase 2 clinical trial showing monotherapy with sotorasib resulted in anti-tumor activity and a favorable benefit-risk profile among heavily pretreated patients with advanced colorectal cancer (Press release, City of Hope, DEC 14, 2021, View Source [SID1234597147]). The research was published today in Lancet Oncology.

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Colorectal cancer is the third most common cancer diagnosed in the United States and the second leading cause of cancer death, according to the Centers for Disease Control and Prevention.

The research study focused on a subset of colorectal cancer patients who carry a mutated gene called KRAS G12C, which is estimated to inflict about 4% of people with colorectal cancer tumors, said Marwan Fakih, M.D., lead study author and co-director of the Gastrointestinal Cancer Program at City of Hope. KRAS mutations have been linked to worse overall survival in colorectal cancer, partly because they are resistant to targeted therapies that inhibit the EGFR protein, a pathway that enables cancer cell growth.

"For this chemotherapy-resistant population, the study results exceeded the historic benefits linked to approved third- and fourth-line therapies for advanced colorectal cancer," said Fakih, professor in City of Hope’s Department of Medical Oncology & Therapeutics Research and the Judy & Bernard Briskin Distinguished Director of Clinical Research. "This Lancet Oncology study is a proof of principle that targeting KRAS G12C with a small molecule KRAS G12C inhibitor, sotorasib, can lead to tumor shrinkage and meaningful duration of disease control in a patient population that otherwise has very limited treatment options."

While the response rate in the study did not meet expectations, the ongoing, single-arm Phase 2 CodeBreaK 100 trial showed an objective response rate of 9.7% among the 62 patients enrolled, with six patients achieving a partial response. Disease control (complete response, partial response or stable disease) was achieved in 82% of patients. Median progression-free survival and overall survival were four months and nearly 11 months, respectively.

Patients had received a median of three prior treatment regimens of systemic anti-cancer therapy, with 73% of patients receiving three or more previous lines of treatment prior to participating in this study. Most treatment-related side effects were minor (grade 1-2) and included diarrhea and nausea.

"These data from the Phase 2 CodeBreaK 100 show encouraging clinical activity and a positive benefit-risk profile with sotorasib in advanced colorectal cancer in this heavily pretreated patient population, with the response rate exceeding the current standard of care therapies," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Amgen remains deeply committed to bringing new treatment options to colorectal cancer patients who harbour the KRAS G12C mutation, and we believe the path forward is combination therapy, so we look forward to investigating sotorasib in combination with panitumumab in our Phase 3 trial."

Currently, overall response rate for patients with recurrent metastatic colorectal cancer who take approved options, such as trifluridine and regorafenib, ranges from 1-4%, Fakih said. Their estimated median progression-free survival and overall survival range from two to three months and six to nine months, respectively. The CodeBreaK 100 data for this patient population demonstrates better response rate and longer survival than current approved medicines.

"We are now working on potentially improving the efficacy of sotorasib by combining it with panitumumab, therefore resulting in a more complete blockade of the EGFR pathway and improving oncological outcomes. We have recently reported the preliminary results of a sotorasib plus panitumumab combination therapy in KRAS G12C mutated metastatic colorectal cancer, which resulted in an overall response rate of 33% in patients who have never received sotorasib," said Fakih. "We are looking forward to the launch and completion of a randomized Phase 3 clinical trial to test and potentially confirm the superiority of sotorasib and panitumumab over standard of care and to enable the approval of this combination in this patient population with unmet needs."

The ongoing clinical trial can be found on ClinicalTrials.gov.

The study, "Sotorasib for previously treated colorectal cancers with KRAS p.G12C mutation (CodeBreaK100): an interim analysis of a single-arm, Phase 2 trial," was supported by industry sponsor Amgen Inc.

On December 14, 2021 Geron Corporation (Nasdaq: GERN), a late-stage biopharmaceutical company focused on the development and commercialization of treatments for hematologic malignancies, reported three poster presentations related to imetelstat, the Company’s first in class telomerase inhibitor, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Geron, DEC 14, 2021, View Source [SID1234597146]). The posters are available at www.geron.com/r-d/publications.

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"The posters for this year’s ASH (Free ASH Whitepaper) Meeting highlight our ongoing Phase 3 development of imetelstat in lower risk MDS and refractory MF, as well as exploratory work in new indications to maximize the potential value of imetelstat," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "We believe the unique telomerase inhibition MOA of imetelstat has the potential to transform the standard of care in hematologic malignancies."

Clinical Posters

Lower Risk Myelodysplastic Syndromes (MDS)

Abstract Title: On-Target Activity of Imetelstat Correlates with Clinical Benefits, Including Overall Survival (OS), in Heavily Transfused Non-Del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) Abstract #2598

The poster reports new analyses to assess the correlation between imetelstat’s inhibition of telomerase with the efficacy and safety data from the IMerge Phase 2 clinical trial. These correlative analyses indicating that patients who achieved optimal pharmacodynamic (PD) effect achieved higher rates of red blood cell transfusion independence (RBC-TI), longer RBC-TI and a trend toward improved overall survival. Importantly, these patients did not have higher rates of Grade 3+ neutropenia, thrombocytopenia or liver function elevations compared to patients who did not achieve optimal PD effect.

These data provide further evidence for the on-target mechanism of action (MOA) of imetelstat through telomerase inhibition and links imetelstat’s on-target activity with clinical benefits.

To confirm these and other results from IMerge Phase 2, the Company is conducting a double-blind, randomized, placebo-controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 170 transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS), also referred to as lower risk MDS, who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint is the rate of RBC-TI for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

IMerge Phase 3 is fully enrolled and patient enrollment has been closed. Based on current planning assumptions, the Company expects top-line results from IMerge Phase 3 in early January 2023.

Refractory Myelofibrosis (MF)

Abstract Title: A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy (BAT) in Patients with Intermediate-2 (Int-2) or High-risk Myelofibrosis (MF) Refractory to Janus Kinase Inhibitor (JAKi) Abstract #1503 Trials in Progress

IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is planned to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis who are refractory to prior treatment with a JAK inhibitor, also referred to as refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete response, partial response, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

IMpactMF is currently enrolling patients. For further information about IMpactMF, including enrollment criteria, locations and current status, visit ClinicalTrials.gov/NCT04576156.

Pre-Clinical Poster – Pediatric Acute Myeloid Leukemia

Abstract Title: Imetelstat Significantly Reduces Leukemia Stem Cells in Patient-Derived Xenograft Models of Pediatric AML Abstract #3352

Acute myeloid leukemia (AML) is the deadliest malignancy in children. To improve survival in pediatric AML, novel targeted therapies and other alternative treatment methods are needed. Due to the significant unmet medical need in this disease, the use of imetelstat was evaluated to determine whether the drug 1) has anti-leukemia activity and 2) could be used as a therapeutic for pediatric AML.

The poster describes results from pre-clinical studies of imetelstat in pediatric AML cell lines (in vitro studies) and patient derived (PDX) mouse models (in vivo studies). The efficacy of imetelstat either as a single agent or in combination with chemotherapy or azacitidine was also evaluated. In cell line experiments, imetelstat treatment resulted in cell apoptosis/death of leukemia stem cells (LSCs) in a time- and dose-dependent manner and with minimal effect on normal bone marrow samples. In the in vivo studies, imetelstat treatment reduced LSC numbers and prolonged survival in mice. Observations of prolonged survival in mice were also seen when combining imetelstat with chemotherapy or azacitidine.

These data suggest imetelstat may represent an effective therapeutic strategy to target the LSC population in pediatric AML patients.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

On December 14, 2021 Legend Biotech Corporation (NASDAQ: LEGN) ("Legend Biotech"), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications, reported that it intends to offer and sell $300.0 million of American Depositary Shares ("ADSs"), each representing two ordinary shares, in an underwritten public offering. All ADSs to be sold in the proposed offering will be offered by Legend Biotech (Press release, Legend Biotech, DEC 14, 2021, View Source [SID1234597145]). Legend Biotech also intends to grant the underwriters a 30-day option to purchase up to an additional $45.0 million of ADSs sold in the public offering at the public offering price, less underwriting discounts and commissions. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed or the actual size or terms of the offering.

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Morgan Stanley, J.P. Morgan, Jefferies, Piper Sandler & Co. and Barclays are serving as joint book-running managers for the offering. BTIG is serving as a co-manager for the offering.

The ADSs are being offered by Legend Biotech pursuant to an effective shelf registration statement that was previously filed with the Securities and Exchange Commission ("SEC"). The offering is being made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. A copy of the preliminary prospectus supplement can be obtained, when available, from Morgan Stanley & Co. LLC, 180 Varick Street, New York, NY 10014, Attention: Prospectus Department, or by telephone at (866) 718-1649; J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at 866-803-9204 or by email at [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by email at [email protected] or by phone at (877) 821-7388; Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, or by email at [email protected] or by telephone at 1-800-747-3924; or Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or by email at [email protected] or by telephone at (888) 603-5847.

This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction.

On December 14, 2021 Prestige BioPharma and Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, NSEIFSC: DRREDDY, hereafter referred to as "Dr. Reddy’s") reported that the two companies have entered into a binding agreement for an exclusive partnership for the supply and commercialization of Prestige BioPharma’s proposed trastuzumab biosimilar in select countries in Latin America and Southeast Asia (Press release, Prestige BioPharma, DEC 14, 2021, View Source [SID1234597141]).

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Prestige BioPharma’s trastuzumab (HD201) is a proposed biosimilar for the treatment of HER2 +ve breast and metastatic gastric cancer. Trastuzumab targets human epidermal growth factor 2 (HER2). In some types of cancer cells, HER2 is overexpressed and stimulates the growth of the cancer cells. Trastuzumab works by selectively binding to HER2, thereby stopping the growth of these cancer cells.

The license agreement grants Dr. Reddy’s the exclusive rights to commercialize the proposed biosimilar in select countries in Latin America and Southeast Asia. Under this partnership, Prestige BioPharma will be responsible for sustainable commercial supply of HD201 from its manufacturing facilities in Osong, South Korea, while Dr. Reddy’s will be responsible for local registrations, marketing and sales in the licensed territories.

Lisa S. Park, CEO of Prestige BioPharma, commented: "We are delighted to establish a partnership with Dr. Reddy’s for key Latin American and Southeast Asian markets. Dr. Reddy’s is the ideal partner to commercialize our lead biosimilar in these territories. With this collaboration, we look forward to further strengthening the value of our biosimilar programs in global markets."

M.V. Ramana, CEO – Branded Markets (India & Emerging Markets), Dr. Reddy’s, said: "In keeping with our purpose of accelerating access to affordable and innovative medicines, we are happy to bring this life-saving drug to patients in need. Our partnership with Prestige BioPharma will help us combine their established expertise in the area of biosimilars with our commercial strengths and growth ambition in these markets. This is in line with our stated intention to create a portfolio of oncology products and expand our biosimilar offerings in Emerging Markets."

On December 14, 2021 BostonGene Corporation and NEC Corporation (NEC; TSE: 6701) reported a strategic global partnership agreement that will enable the companies to offer BostonGene Tumor PortraitTM Tests in key international markets, including Japan as the first market outside of the U.S (Press release, NEC, DEC 14, 2021, View Source [SID1234597133]).

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BostonGene’s innovative computational platform performs AI-based molecular and immune profiling to discover correlations between tumor genomics, a patient’s immune system and the effectiveness of all available approved and experimental treatments. BostonGene Tumor Portrait Tests, based on integrated genomic and transcriptomic analysis, propel precision medicine into daily clinical practice and support physicians in actualizing personalized therapy for cancer patients.

Moreover, in NEC’s ongoing personalized neoantigen clinical trial that utilizes its AI-driven neoantigen prediction technology, NEC and BostonGene are collaborating to provide molecular characterization of patient tumors. Going forward, the two companies will jointly develop the market for BostonGene Tumor Portrait Tests globally. In Japan, the companies aim to utilize NEC’s healthcare and life science network in order to provide Tumor Portrait Tests to hospitals throughout the country.

In 2020, 378,385 people died of cancer in Japan, according to a Ministry of Health, Labor, and Welfare report. This accounts for 27.6% of all deaths that year and equates to one in four people dying of cancer. Leveraging NEC’s longstanding relationships with cancer centers, pharma and biotech companies, the organizations will work closely together to demonstrate the critical role of next generation multi-platform analytics combined with cutting-edge software to improve the diagnosis and treatment for cancer patients. Earlier this year, NEC announced an initiative to create healthcare and life science business that utilizes AI and other digital technologies as part of the "creation of future growth businesses" set forth in the 2025 Mid-term Management Plan.

"NEC has been committed to contributing to healthcare for more than half a century, which includes state-of-the-art hospital information systems in Japan. Cancer is now the country’s most common cause of death, and NEC has been working with the National Cancer Center Japan since 2016. Today, NEC remains as dedicated as ever to applying our rich experience in AI and analytics for improving patients’ outcomes," said Takayuki Morita, President and CEO at NEC Corporation. "BostonGene’s offering of deep molecular and immune profiling, coupled with its computational power and analytics, have already improved the quality of care for cancer patients in both academic and community settings in the United States. Supporting BostonGene’s international expansion enables us to continue to rapidly drive innovation that improves the standard of care in Japan and abroad."

"NEC has a long history of offering industry leading products and solutions in the field of healthcare both in Japan and globally," said Andrew Feinberg, President and CEO at BostonGene. "Partnering with NEC will allow BostonGene to expedite our international expansion which aims to improve the standard of care for cancer patients around the world."

This agreement expands upon existing collaborations between BostonGene and NEC.